In vivo validation and characterization of allelic variants in lupus identification and characterization of the etiologic and pathogenic mechanisms underlying systemic lupus erythematosus (SLE) are paramount for prevention and treatment of disease and one of its most mortal complications, glomerulonephritis. With the advent of whole genome sequencing came tantalizing allelic variants in patients with systemic lupus erythematosus (SLE); however, a critical barrier to understanding the role of these variants is that their characterization has been limited in vivo, especially in well-characterized mouse models of lupus nephritis. Furthermore, few data exist regarding allelic variants in lupus glomerulonephritis specifically. The goals of this work will be to (1) overcome a critical barrier n the field by creation of an in vivo system of lupus nephritis-prone mice harboring an immune system expressing allelic variants or their respective short hairpin RNA (shRNA) and (2) characterize the effects of allelic variants on disease progression. These studies will provide insight into allelic variants in patients with lupus nephritis and provide even broader impact on the field of autoimmunity as a whole. PUBLIC HEALTH RELEVANCE: Understanding what causes systemic lupus erythematosus (SLE) is paramount for prevention and treatment of the disease and one of its most mortal complications, glomerulonephritis. With the advent of whole genome sequencing came the realization that certain genes are mutated in patients with SLE; however, examination of the result of these mutations on the disease process has been limited. These studies will provide insight into the function of these mutated genes in patients with lupus nephritis and provide even broader impact on the field of autoimmunity as a whole.